Clostridium difficile is the leading cause of antibiotic-associated diarrhoea, causing significant morbidity and mortality. C. difficile produces a paracrystalline 2D array of proteins (S-layer) that completely coats the bacterial surface. The S-layer consists of approx. 500,000 copies of the SlpA protein and is functionalised by an additional 28 related cell wall proteins. Producing the S-layer requires a significant metabolic effort by the bacterium but little is known about its function as the encoding gene, slpA, is essential. In recent years we have identified a dedicated secretion pathway and a number of accessory proteins that are required for assembly of the S-layer. Using 2D electron diffraction we have also begun to build a picture of the C. difficile cell surface. Despite these new insights, functional analysis has been hampered by a lack of isogenic slpA mutants. In collaboration with AvidBiotics (South San Francisco) we have recently isolated a spontaneous slpA mutant that has allowed genetic manipulation of the S-layer for the first time. Using this new tool we have identified pleiotropic functions for the S-layer including resistance to immune effectors and antibiotics, cell wall biogenesis and sporulation.
"Scratching the surface: Biogenesis and function of the C. difficile surface layer"
Thursday, May 5, 2016 - 10:00
MSI Small Lecture Theatre
Professor Nicola Stanley-Wall FRSE FRSB FEAM
Dr Robert Fagan
University of Sheffield